Immunity to infectious diseases.

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Immunity to infectious diseases.

• Prof. Mohamed Osman Gad El Rab.
• College of Medicine KKUH.

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Classification of immunity.

• Acquired immunity.
• active.
  passive.
• natural. artificial. natural.
  artificial.
• infections. immuniz. Maternal immuno
  -
• IgG.
  therapy.

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• Immunity to viral infections .

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• Innate (natural) immunity
• many viruses induce
• 1. production of type 1 interferons.
• ( INF- alpha INF - beta.)
• 2. activation of NK - cells .

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dsRNA produced during viralreplication
induce the expression of interferons by
the infected cells.

• monocytes , macrophages fibroblasts
• also synthesize interferons .

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Viruses initiate infection by binding to
specific host - cell membrane molecules .

• e.g.
• 1. influenza virus bind to cell membrane
• glycoproteins .
• 2. rhinoviruses bind to intercellular
• adhesion molecules (ICAMs).

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Mechanism of action

• Interferons bind to receptors that activate
• JAK-STAT pathways.
• These induce several genes .
• One gene activate a ribonuclease that
• degrade viral RNA .

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2. Other genes activate protein kinases
which inhibit proteinsynthesis .

• 3. binding of INFs to NK-cells induce
• lytic activity .
• IL-12 produced by macrophages also
• enhance NK-cell activity .

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Antibody- mediated immunity

• Anti-viral antibodies
• 1. prevent spread during acute infection.
• 2. protect against reinfection .

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Protective functions of antibodies

• 1. secretory IgA blocks viral attachment .
• 2. complement - fixing antibodies may
• cause lysis of enveloped viruses
• 3.IgM antibody agglutinate viral particles .

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Cell mediated immunity is important for
control clearance of viral infections .

• CTL activity arises within 3 - 4 days,
• peak by 7-10 days then decline
• when the infection is cleared .

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Viruses can evade host defenses.

• 1. Hepatitis C virus
• overcome anti - viral effect of INFs
• blocking the action of protein kinase.
• 2.Adenoviruses CMV
• reduce surface expression of MHC-1.

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3. Measles ,CMV HIV reduce MHC
-11 levels .

• 4. A large no. of viruses cause
• generalized immunosuppression.
  .
• e.g. mumps , measles , EBV., CMV.,
• HIV.

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Influenza virus .
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Antigenic variation of influenzavirus .

• In 1918-1919 an influenza pandemic
• killed over 20 million people .
• The structure of the virus contain
• Hemagglutinins (HA ).
• Neuraminidase (NA ).

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Shifting Nature of Influenza

• Antigenic drift small, ceaseless changes in the
  genetic structure. New strains continually
  replace old strains.
• Antigenic shift major change, usually occurs
  when species hosting virus trade viral genes.
  Novel strain appears without natural immunity in
  host population.

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1. Antigenic drift gradual minor change in HA
NA.

• 2. Antigenic shift
• sudden major change in HA NA .
• ( new subtype emerge )

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1918 Hemagglutinin Causes Severe Lung Damage.
M88/Hsp
M88
Kobasa et al. Nature 2004431703
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• Immunity to bacterial infections.

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• If the inoculum (dose ) is small and the
• virulence of the bacteria is low .
• Tissue phagocytes may eliminate
• the bacteria .

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The humoral response (antibody) is the
main protective response against
extracellular bacteria .

• Antibodies act in several ways
• 1. neutralize toxins .
• 2.activate complement .
• - generates anaphylatoxins.
• -release chemotactic agents
  .

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Protective functions of antibodies.
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Intracellular bacteria

• Initially activate NK cells which
• provide early defense .
• Final control is by
• cell - mediated immunity .
• ( this involve activated macrophages )

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Cell-mediated immunity involve activated
macrophages.
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Bacteria can by-pass host defense

• 4 steps in bacterial infections
• 1. attachment .(adherence).
• 2. proliferation .
• 3. invasion of host tissues .
• 4. toxin - induced damage.

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Adherence
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Penetration into the Host Cell
Salmonella entering epithelial cells via invasins
Figure 15.2
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Secretory IgA block attachment , but some
bacteria secrete proteases that break IgA .

• Opsonization phagocytosis prevent
• proliferation , but some bacterial
  surface structures inhibit phagocytosis,
• ( polyssacharide capsule ,Strp.pneum.)

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Strep.pneumonae. Inhibit phagocytosis.
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3. Some bacteria resist complement lysis .

• 4. Mycobacteria survive intracellularly by
• resisting oxidative attack ,some prevent
• lysosomal fusion .

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Complications of immune responses .

• In some cases disease is not caused by
• the bacteria but rather by the immune
• response.

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Endotoxins of gram ve bacteriaactivate
macrophages which releasehigh levels of
IL-1, TNF - alpha, these may cause
Septic shock .

• In staphylococcal food poisoning ,
• enterotoxins act as superantigens
• and cause direct massive T-cell
  activation . This may cause
• Toxic shock syndrome .

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Endotoxin
Contrast the nature and effects of exotoxins and
endotoxins.
Figure 15.4b
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Exotoxins
Figure 15.4a
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3.Complications of streptococcus pyogenes
throat infections

• 1. Rheumatic fever antibodies formed against
  antigen in the strep. cell wall cross react with
  the sacrolemma of
• Human heart .Granuloma form in the heart
  (Aschoffs
• nodules).
• 2. Rheumatic heart disease repeated attacks
  by strep. with different M types can
  result in damage to the heart valves.( certain
  children have a genetic predisposition
• to this immune-mediated disease ). ( high
  A.S.O. titer ).

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• 3. Acute glomerulonephritis
• antibodies to strep . components combine to
  form
• immune- complexes which then deposit in the
  kidney
• glomeruli .

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4. In chronic intracellular infections e.g.
T.B. excessive CMI responses lead to
granuloma formation .
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Granuloma formation ( T.B. )
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The balance between TH1 TH2 is
important in immunity. It determine
the clinical presentation of the
disease .
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5. Immunological response in leprosy

• The response decide the type of disease
• 1.In tuberculoid leprosy the patient mount an
  effective
• cell-mediated response.Macrophages destroy the
  bacilli
• and contain the infection .
• 2. In lepromatous leprosy the patient is unable
  to produce
• a cell-mediated response and organisms
  multiply and
• spread in the tissues gt

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• Immunity to parasitic infections

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• A. Protozoal diseases .
• These are unicellular organisms .
• e.g. malaria , trypansomiasis , toxoplasma,
• They have complex life - cycles.
• some stages are free in the blood ,
• other stages are intracellular.

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The type of the immune response depend
on the location of the
parasite in the host .

• In the blood antibodies may be effective
• In the intracellular stage CMI may be
• effective.

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Immunity to Malaria

• Caused by genus Plasmodium.
• P.falciparum is the most virulent
  prevalent.
• Infect 10 of the population.
• Causes 1 2 million deaths every year.
• Have a complex life cycle .

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Life cycle of malaria
3-stages.
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During the life- cycle, many antigensappear

• Infection begin with mosquito bite.
• Sporozoites enter the blood disappear
• within 30 min.
• Migrate to the liver after 1
  week
• release merozoites which infect RBCs.

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Sporozoites stay for only 30 min. in the
blood, therefore induce a poor immune
response.

• The intracellular stage in the liver cells
• and RBC ,reduce the degree of immune
• activation generated by the pathogen.

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In endemic areas

• Only 22 of the children have detectable
• antibodies to sporozoites.
• In adults 84 have such antibodies.
• In general, the degree of immunity to
• Malaria is not complete .

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Trypansomiasis ( sleeping sickness).

• As the parasite multiply , an
  effective
• antibody response develop to
  the
• glycoprotein coat called variant
  surface
• glycoprotein (VSG).
• These antibodies eliminate most of
  the
• Parasite from the blood
  by
• 1. complement lysis.
• 2. opsonization
  phagocytosis .

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Trypansomes, (T. cruz,)
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However , 1 of the parasite with
differentantigen (VSG ) escape the
antibody response. These
proliferate and a new wave of
parasites invade the blood .

• This is called antigenic shifts.
• (a characteristic feature of
  Trypansomes ).

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Immunity to parasitic worms (helminths)

• Helminths are large multicellular
  organisms e.g. Schistosoma (Bilharzia ).
• Have complex life- cycle .
• Cercaria enter the blood stream and
  become schistosomules which enter
• capilleries.then pass to the lungs
  liver.
• then become adult worms.

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Immune responses are not sufficient
to eliminate the adult worms .

• Adult worms evade immune responses
• by coating themselves by host
• glycoproteins .

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Humoral immune responses to parasitesare
characterized by

• 1. elevated IgE.
• 2. blood eosinophilia .
• Eosinophils mediate ADCC to
• damage the parasite.

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A chronic state develop in which
adultworms persist and induce
cell-mediated delayed hypersensitivity
reactions

• This eventually result in the formation of
• large granulomas .

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• Immunity to fungi .

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• Fungal infections of man fall into 4 types
• 1.superficial mycoses .
• 2.subcutaneous mycoses.
• 3.respiratory mycoses.
• 4.candida albicans .
• Recovery is based on cell-mediated immunity.
• There is also evidence for neutrophil involvement
• In immunity to some respiratory mycoses.

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Immunology quiz no 4.
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A.

• A12-year old girl has been receiving cytotoxic
  drugs for
• Acute leukemia. Although there is evidence
  that the leukemia is responding, she has become
  neutropenic
• ( neutrophils were less than 0.5 x10 ml )
  .Early in the evening she was found to have
  fever, within half an hour
• she collapsed and was found to have features
  of sock
• (tachycardia and hypotention ).
• Blood was taken for culture which later grew
  E. coli. She
• was started on antibiotics and fluid
  replacement .She
• gradually improved during the next 12 hours .

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1. What is the diagnosis of this patient
?2. What is the predominant cell
involved in this condition ?

• 2. Describe the underlying
  immunopathology.?

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B.

• What is the recommended childhood immunization
• schedule in Saudi Arabia ?
• What are the indications for passive
  immunization ?
• Mention 2 infectious and 1 non-infectious
  condition
• for which passive immunization may be
  required ?

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Practical points
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• Routine tests in microbial serology .
• 1. Widal test for diagnosis of typhoid fever.
• standard tube agglutination test (STA)
• -patient serum in dilution mixed with
• salmonella suspension .
• 2.A.S.O. test.
• anti- streptolysin O test.
• -toxin anti-toxin neutrallization test for
• diagnosis of streptococcal infections .
• (patient serum neutralize toxin therefore
  indicator R.B.C . not lysed )

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3. T.P.H.A.test.

• Treponema pallidum hemagglutination test.
• -for diagnosis of syphilis.

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Trypansomes,life cycle.